Project Summary/Abstract HCV infection is the most common chronic blood-borne infection in the U.S., with the overwhelming majority of new HCV infections occurring among people who inject drugs (PWID). Sharing syringes and other injection equipment is the primary risk factor for HCV transmission. HCV prevalence is extremely high in most U.S. PWID populations (typically ranging from ~40-70%). Research shows that young PWID (under age 30) engage in particularly high rates of risky injection, and that HCV incidence is highest in the first 3-5 years of an individual's injection career. The national significance of this public health problem is heightened by the recent epidemic of prescription opioid (PO) misuse in youth which has evolved into widespread heroin use and injection drug use, creating a new generation of young injectors at risk for HCV and HIV. These trends demonstrate the urgent need for innovative new approaches to HCV prevention tailored to the growing population of young PWID. To date, no behavioral intervention has been sufficiently potent to produce significant reductions in HCV incidence in at-risk groups of PWID. To address this critical gap, our team developed Staying Safe (Ssafe), an innovative, strengths-based, socio-behavioral HCV prevention intervention for young PWID. Ssafe addresses multi-level ?upstream? determinants of risk that occur relatively early in the causal chain of risk, including eco-social conditions, social relations and risk situations, in addition to directly targeting risky injection practices. Ssafe trains and motivates PWID to better manage drug use in order to avoid situations and practices that promote risky injection (e.g., ?binging? on drugs), and to implement health- protective behaviors (e.g., promoting risk-reduction norms in injection networks). In preliminary research we found Ssafe to be highly acceptable and feasible, with strong indications of efficacy. In this study we propose to conduct a randomized, controlled trial to assess the effectiveness of the Ssafe intervention (with a mobile phone-delivered booster application) in reducing injection-related risk behavior and HCV incidence among 18- 29 year-olds (n=456) who inject opioids (heroin and/or POs) and test HCV and HIV antibody-negative at baseline. We hypothesize that Ssafe will significantly reduce injection risk behaviors and HCV infections relative to a time- and attention-matched control intervention. We will also examine whether Ssafe's effects are mediated by (a) drug use management practices (injection frequency, drug intake, opioid withdrawal episodes); (b) individual-level mechanisms of behavior change (motivation/self-efficacy, planning skills); and (c) key upstream socio-structural and network-level determinants of risk (social support, skills to avoid PWID- associated stigma, drug treatment and SEP utilization, injection network size and risk norms). The proposed trial promises to significantly advance our ability to prevent HCV infection in the growing population of young, PO-initiated injectors.